The heightened release of ACTH from th anterior pituitary in response to stressful stimuli is, in a large part, dependent upon the synergistic actions of corticotropin-releasing hormone (CRH), vasopressin (VP), and oxytocin (OXY). The activation of parvocellular neurons that colocalize VP and CRH and terminate in the external zone of the median eminence is thought to be the major neuroendocrine pathway for stress-evoked release of ACTH. However, there is evidence that the magnocellular VP and OXY system, whose fibers pass through the internal zone of the median eminence to terminate in the neurohypophysis, may contribute to the VP and OXY measured in the portal circulation, and to the potentiation of CRH-induced ACTH release during stress. Until now, there has been no experimental model that would allow the parvocellular system to be studied independent of the magnocellular system. However, it was discovered that the magnocellular system can be eliminated in hamsters by microinjecting the suicide transport lectin volkensin into the neurohypophysis. With this new model we will examine the functional significance of the magnocellular VP and OXY system in the control of ACTH release during stress by: (1) comparing the levels of VP and OXY in the portal circulation in hamsters microinjected into the neurohypophysis with volkensin or saline vehicle, and (2) comparing the levels of ACTH, cortisol, VP and OXY in the systemic circulation in hamsters microinjected with volkensin or saline vehicle in response to: (A) brief exposure to ether, (B) insulin-induced hypoglycemia, (C) exposure to low ambient temperatures, and (D) aggressive encounters between conspecifics. These studies will provide a unique opportunity to examine the functional interaction between the parvocellular and magnocellular systems in the neuroendocrine regulation of ACTH secretion, and should enhance our understanding of the neural organization, activation, and interaction of CRH, VP, and OXY neurons that contribute to adaptive responding during stress.